The spermostatic and microbicidal actions of quinones and malemides : towards a dual-purpose contraceptive agent

There is an urgent need to develop safe, effective, dual-purpose contraceptive agents that combine the prevention of pregnancy with protection against sexually transmitted diseases. Here we report the identification of a group of compounds that on contact with human spermatozoa induce a state of “spermostasis,” characterized by the extremely rapid inhibition of sperm movement without compromising cell viability. These spermostatic agents were more active and significantly less toxic than the reagent in current clinical use, nonoxynol 9, giving therapeutic indices (ratio of spermostatic to cytotoxic activity) that were orders of magnitude greater than this traditional spermicide. Although certain compounds could trigger reactive oxygen species generation by spermatozoa, this activity was not correlated with spermostasis. Rather, the latter was associated with alkylation of two major sperm tail proteins that were identified as A Kinase-Anchoring Proteins (AKAP3 and AKAP4) by mass spectrometry. As a consequence of disrupted AKAP function, the abilities of cAMP to drive protein kinase A-dependent activities in the sperm tail, such as the activation of SRC and the consequent stimulation of tyrosine phosphorylation, were suppressed. Furthermore, analysis of microbicidal activity using Chlamydia muridarum revealed powerful inhibitory effects at the same low micromolar doses that suppressed sperm movement. In this case, the microbicidal action was associated with alkylation of Major Outer Membrane Protein (MOMP), a major chlamydial membrane protein. Taken together, these results have identified for the first time a novel set of cellular targets and chemical principles capable of providing simultaneous defense against both fertility and the spread of sexually transmitted disease.

Identification of area-level influences on regions of high cancer incidence in Queensland, Australia : a classification tree approach

Background: Strategies for cancer reduction and management are targeted at both individual and area levels. Area-level strategies require careful understanding of geographic differences in cancer incidence, in particular the association with factors such as socioeconomic status, ethnicity and accessibility. This study aimed to identify the complex interplay of area-level factors associated with high area-specific incidence of Australian priority cancers using a classification and regression tree (CART) approach. Methods: Area-specific smoothed standardised incidence ratios were estimated for priority-area cancers across 478 statistical local areas in Queensland, Australia (1998-2007, n=186,075). For those cancers with significant spatial variation, CART models were used to identify whether area-level accessibility, socioeconomic status and ethnicity were associated with high area-specific incidence. Results: The accessibility of a person’s residence had the most consistent association with the risk of cancer diagnosis across the specific cancers. Many cancers were likely to have high incidence in more urban areas, although male lung cancer and cervical cancer tended to have high incidence in more remote areas. The impact of socioeconomic status and ethnicity on these associations differed by type of cancer. Conclusions: These results highlight the complex interactions between accessibility, socioeconomic status and ethnicity in determining cancer incidence risk.

The Long-Term Irrelevance of Trust in Outsourcing Decisions for New Technologies: Insights from an Agent-Based Model

Significant empirical data from the fields of management and business strategy suggest that it is a good idea for a company to make in-house the components and processes underpinning a new technology. Other evidence suggests exactly the opposite, saying that firms would be better off buying components and processes from outside suppliers. One possible explanation for this lack of convergence is that earlier research in this area has overlooked two important aspects of the problem: reputation and trust. To gain insight into how these variables may impact make-buy decisions throughout the innovation process, the Sporas algorithm for measuring reputation was added to an existing agent-based model of how firms interact with each other throughout the development of new technologies. The model�s results suggest that reputation and trust do not play a significant role in the long-term fortunes of an individual firm as it contends with technological change in the marketplace. Accordingly, this model serves as a cue for management researchers to investigate more thoroughly the temporal limitations and contingencies that determine how the trust between firms may affect the R&D process.

Using incomplete online metric maps for topological exploration with the Gap Navigation Tree

This paper presents a general, global approach to the problem of robot exploration, utilizing a topological data structure to guide an underlying Simultaneous Localization and Mapping (SLAM) process. A Gap Navigation Tree (GNT) is used to motivate global target selection and occluded regions of the environment (called “gaps”) are tracked probabilistically. The process of map construction and the motion of the vehicle alters both the shape and location of these regions. The use of online mapping is shown to reduce the difficulties in implementing the GNT.

Teachers’ perceptions of the use of an external change agent in school curriculum change

An external change agent (ECA) was recently employed in three Queensland schools to align the school curriculum with the requirements of the state’s high stakes test known as the Queensland Core Skills test (QCS). This paper reports on the teachers’ perceptions of a change process led by an ECA. With the ever-increasing implementation of high stakes testing in Australian schools, teachers are under mounting pressure to produce ‘results’. Therefore, in order to maximise their students’ success in these tests, schools are altering their curricula to incorporate the test requirements. Rather than the traditional method of managing such curriculum change processes internally, there is a growing trend for principals to source external expertise in the form of ECAs. Although some academics, teachers, and much of the relevant literature, would regard such a practice as problematic, this study found that in fact, teachers were quite open to externally led curriculum change, especially if they perceived the leader to be knowledgeable and creditable in this area.

Minimizing information leakage of tree-based RFID authentication protocols using alternate tree-walking

The privacy of efficient tree-based RFID authentication protocols is heavily dependent on the branching factor on the top layer. Indefinitely increasing the branching factor, however, is not a viable option. This paper proposes the alternate-tree walking scheme as well as two protocols to circumvent this problem. The privacy of the resulting protocols is shown to be comparable to that of linear-time protocols, where there is no leakage of information, whilst reducing the computational load of the database by one-third of what is required of tree-based protocols during authentication. We also identify and address a limitation in quantifying privacy in RFID protocols.